Targeted fishing of invasive lionfish (Pterois volitans and P. miles) in the Caribbean creates an opportunity to monitor lionfish for food safety and to examine their utility as environmental sentinel species. The goals of this study were to assess P. volitans for histamine toxicity (scombroid poisoning) and to quantify mineral and heavy metal contaminants in lionfish in Grenada, West Indies. Histamine concentrations in lionfish muscle significantly increased after heat stress but remained below maximum allowable concentrations for consumption. Mineral and heavy metal concentrations were tested in muscle and liver from lionfish from two separate reef systems using inductively coupled plasma–mass spectrometry. Total arsenic levels in liver were significantly higher in fish sampled from Boss's Reef than those from Halifax Harbor, but they were not interpreted as clinically significant. Lead, mercury, cadmium, copper, molybdenum, and cobalt were below the detectable limit of the analyzer. Thallium, selenium, iron, zinc, and manganese were detected in muscle and/or liver tissue at expected concentrations. Lionfish represent a low risk for histamine toxicity and have not bioaccumulated significant heavy metals in Grenada to pose a food safety risk. The higher arsenic concentrations in Boss's Reef suggest that the location should be monitored and studied in the future. The potential for lionfish to act as bioindicators for heavy metals is uncertain and needs further validation.